Zhao Hongmei, Zhou Juan, Yuan Lingzhi, Sun Zhiyi, Liu Yi, Zhao Xinyu, Ye Feng
Department of Infectious Disease, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Gastroenterology and Nutrition, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, China.
Front Microbiol. 2025 Jan 7;15:1518150. doi: 10.3389/fmicb.2024.1518150. eCollection 2024.
This study investigates the protective effects of lactic acid, a metabolite of , on non-alcoholic fatty liver disease (NAFLD) induced by a high-sugar, high-fat diet (HFD) in mice, in the context of the gut-liver axis.
A NAFLD mouse model was established using a HFD, and different intervention groups were set up to study the protective effects of and its metabolite lactic acid. The groups included a control group, NAFLD group, treatment group, Glyceraldehyde-3-P (G-3P) co-treatment group, and NOD-like receptor family pyrin domain containing 3 (NLRP3) overexpression group. The evaluation of liver function and lipid metabolism was conducted using the liver-to-body weight ratio, histological staining, and biochemical assays. Enzyme-linked immunosorbent assay (ELISA) was performed to measure inflammatory cytokines, and western blotting was used to analyze the expression of NLRP3 inflammasome and autophagy-related molecules. , an NAFLD cell model was established using oleic acid, with cells treated with lactic acid and NLRP3 overexpression to assess lipid droplet accumulation and inflammation.
findings indicated that, in comparison to CBX group (Control group without antibiotic treatment), NAFLD/CBX group (NAFLD group without antibiotic administration) and NAFLD/ABX group (NAFLD group with antibiotic administration) exhibited increased liver-to-body weight ratio, higher lipid droplet accumulation, aggravated liver histopathological damage, and elevated levels of AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase), TC (Total Cholesterol), TG (Triglycerides), LDL-C (Low-Density Lipoprotein Cholesterol), IL-6 (Interleukin-6), TNF-α (Tumor Necrosis Factor-alpha), IL-1β (Interleukin-1 beta), and NLRP3-related molecules, while HDL-C (High-Density Lipoprotein Cholesterol) levels significantly decreased. Intervention with significantly reversed these adverse changes. Further addition of G-3P led to more pronounced improvement in NAFLD symptoms, while overexpression of NLRP3 weakened the protective effects of . results indicated that Ole group exhibited heightened lipid droplet accumulation and expression of NLRP3 inflammasome-related molecules relative to the control group. Treatment with lactic acid effectively reversed these changes; however, the protective effect of lactic acid was significantly weakened with NLRP3 overexpression.
Lactic acid can alleviate lipid metabolism disorders in NAFLD induced by diet through the inhibition of inflammation mediated by the NLRP3 inflammasome and the regulation of the autophagy process.
本研究在肠-肝轴的背景下，探讨3-磷酸甘油醛（G-3P）的代谢产物乳酸对高糖高脂饮食（HFD）诱导的小鼠非酒精性脂肪性肝病（NAFLD）的保护作用。
采用HFD建立NAFLD小鼠模型，并设置不同干预组以研究G-3P及其代谢产物乳酸的保护作用。这些组包括对照组、NAFLD组、G-3P治疗组、Glyceraldehyde-3-P（G-3P）联合治疗组和含3的NOD样受体家族吡啉结构域（NLRP3）过表达组。使用肝重与体重比、组织学染色和生化测定来评估肝功能和脂质代谢。进行酶联免疫吸附测定（ELISA）以测量炎性细胞因子，并使用蛋白质免疫印迹法分析NLRP3炎性小体和自噬相关分子的表达。此外，使用油酸建立NAFLD细胞模型，用乳酸和NLRP3过表达处理细胞以评估脂滴积累和炎症。
研究结果表明，与CBX组（未用抗生素治疗的对照组）相比，NAFLD/CBX组（未给予抗生素的NAFLD组）和NAFLD/ABX组（给予抗生素的NAFLD组）的肝重与体重比增加、脂滴积累更高、肝组织病理学损伤加重，并且天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和NLRP3相关分子水平升高，而高密度脂蛋白胆固醇（HDL-C）水平显著降低。用G-3P干预可显著逆转这些不良变化。进一步添加G-3P导致NAFLD症状更明显改善，而NLRP3过表达减弱了G-3P的保护作用。细胞实验结果表明，与对照组相比，Ole组的脂滴积累和NLRP3炎性小体相关分子的表达增加。用乳酸处理可有效逆转这些变化；然而，随着NLRP3过表达，乳酸的保护作用显著减弱。
乳酸可通过抑制NLRP3炎性小体介导的炎症和调节自噬过程来减轻饮食诱导的NAFLD中的脂质代谢紊乱。
